{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:35:29Z","timestamp":1774647329059,"version":"3.50.1"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2015,10,28]],"date-time":"2015-10-28T00:00:00Z","timestamp":1445990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0141452","type":"journal-article","created":{"date-parts":[[2015,10,28]],"date-time":"2015-10-28T16:32:05Z","timestamp":1446049925000},"page":"e0141452","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":26,"title":["Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit"],"prefix":"10.1371","volume":"10","author":[{"given":"Theodora","family":"Nikolaidou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue J.","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert S.","family":"Stephenson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Yanni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tristan","family":"Lowe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Atkinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline B.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rida","family":"Sardar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio F.","family":"Corno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Halina","family":"Dobrzynski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip J.","family":"Withers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan C.","family":"Jarvis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Hart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark R.","family":"Boyett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2015,10,28]]},"reference":[{"key":"ref1","unstructured":"Chronic Heart Failure: The Management of Adults with Chronic Heart Failure in Primary and Secondary Care (Partial Update). National Institute for Health and Clinical Excellence, 2010. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.nice.org.uk\/guidance\/cg108\/resources\/guidance-chronic-heart-failure-pdf\" xlink:type=\"simple\">http:\/\/www.nice.org.uk\/guidance\/cg108\/resources\/guidance-chronic-heart-failure-pdf<\/ext-link>"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"2802","DOI":"10.1161\/01.CIR.0000146785.15995.67","article-title":"From mouse to whale: a universal scaling relation for the PR Interval of the electrocardiogram of mammals","volume":"110","author":"SF Noujaim","year":"2004","journal-title":"Circulation"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1093\/eurjhf\/hfp074","article-title":"Surface electrocardiogram to predict outcome in candidates for cardiac resynchronization therapy: a sub-analysis of the CARE-HF trial","volume":"11","author":"R Gervais","year":"2009","journal-title":"Eur J Heart Fail"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1161\/01.CIR.80.6.1675","article-title":"Diverse mechanisms of unexpected cardiac arrest in advanced heart failure","volume":"80","author":"M Luu","year":"1989","journal-title":"Circulation"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.hrthm.2011.07.038","article-title":"Does cardiac resynchronization therapy provide unrecognized benefit in patients with prolonged PR intervals? The impact of restoring atrioventricular synchrony: an analysis from the COMPANION Trial","volume":"9","author":"B Olshansky","year":"2012","journal-title":"Heart Rhythm"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1001\/jama.2009.888","article-title":"Long-term outcomes in individuals with prolonged PR interval or first-degree atrioventricular block","volume":"301","author":"S Cheng","year":"2009","journal-title":"JAMA"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1161\/01.CIR.0000139336.69955.AB","article-title":"Remodeling of sinus node function in patients with congestive heart failure: reduction in sinus node reserve","volume":"110","author":"P Sanders","year":"2004","journal-title":"Circulation"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1161\/01.CIR.0000083719.51661.B9","article-title":"Ionic remodeling of sinoatrial node cells by heart failure","volume":"108","author":"AO Verkerk","year":"2003","journal-title":"Circulation"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.cardiores.2005.02.011","article-title":"Sinus node dysfunction and hyperpolarization-activated (HCN) channel subunit remodeling in a canine heart failure model","volume":"66","author":"S Zicha","year":"2005","journal-title":"Cardiovasc Res"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1161\/CIRCHEARTFAILURE.110.957647","article-title":"Changes in ion channel gene expression underlying heart failure-induced sinoatrial node dysfunction","volume":"4","author":"J Yanni","year":"2011","journal-title":"Circ Heart Fail"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1161\/01.CIR.0000090688.49283.67","article-title":"Electrical remodeling of the atria in congestive heart failure: electrophysiological and electroanatomic mapping in humans","volume":"108","author":"P Sanders","year":"2003","journal-title":"Circulation"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1161\/01.CIR.101.22.2631","article-title":"Effects of experimental heart failure on atrial cellular and ionic electrophysiology","volume":"101","author":"D Li","year":"2000","journal-title":"Circulation"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.yjmcc.2004.12.012","article-title":"Increased late sodium current in myocytes from a canine heart failure model and from failing human heart","volume":"38","author":"CR Valdivia","year":"2005","journal-title":"J Mol Cell Cardiol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.hrthm.2004.06.003","article-title":"Ionic current abnormalities associated with prolonged action potentials in cardiomyocytes from diseased human right ventricles","volume":"1","author":"GR Li","year":"2004","journal-title":"Heart Rhythm"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1161\/01.RES.0000093399.11734.B3","article-title":"Elevated sarcoplasmic reticulum Ca<sup>2+<\/sup> leak in intact ventricular myocytes from rabbits in heart failure","volume":"93","author":"TR Shannon","year":"2003","journal-title":"Circ Res"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1161\/CIRCRESAHA.108.172403","article-title":"Computer three-dimensional reconstruction of the atrioventricular node","volume":"102","author":"J Li","year":"2008","journal-title":"Circ Res"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1161\/01.RES.4.4.357","article-title":"Physiologic evidence for a dual A-V transmission system","volume":"4","author":"GK Moe","year":"1956","journal-title":"Circ Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1002\/ar.20631","article-title":"Connexin 43 expression delineates two discrete pathways in the human atrioventricular junction","volume":"291","author":"WJ Hucker","year":"2008","journal-title":"Anat Rec (Hoboken)"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1161\/01.RES.0000101913.95604.B9","article-title":"Site of origin and molecular substrate of atrioventricular junctional rhythm in the rabbit heart","volume":"93","author":"H Dobrzynski","year":"2003","journal-title":"Circ Res"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1161\/CIRCEP.108.803569","article-title":"Ion channel transcript expression at the rabbit atrioventricular conduction axis","volume":"2","author":"ID Greener","year":"2009","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"e35299","DOI":"10.1371\/journal.pone.0035299","article-title":"Contrast enhanced micro-computed tomography resolves the 3-dimensional morphology of the cardiac conduction system in mammalian hearts","volume":"7","author":"RS Stephenson","year":"2012","journal-title":"PLoS ONE"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3389\/fped.2013.00033","article-title":"Congestive heart failure: experimental model","volume":"1","author":"AF Corno","year":"2013","journal-title":"Front Pediatr"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1109\/TMI.2012.2209183","article-title":"Application of micro-computed tomography with iodine staining to cardiac imaging, segmentation, and computational model development","volume":"32","author":"OV Aslanidi","year":"2013","journal-title":"IEEE Trans Med Imaging"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3389\/fped.2013.00026","article-title":"Studying the microanatomy of the heart in three dimensions: a practical update","volume":"1","author":"JC Jarvis","year":"2013","journal-title":"Front Pediatr"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/(SICI)1522-2683(20000101)21:1<128::AID-ELPS128>3.0.CO;2-M","article-title":"A microfluidic system for high-speed reproducible DNA sizing and quantitation","volume":"21","author":"O Mueller","year":"2000","journal-title":"Electrophoresis"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/gkp045","article-title":"Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data","volume":"37","author":"JM Ruijter","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"e12336","DOI":"10.1371\/journal.pone.0012336","article-title":"Should we abandon the t-test in the analysis of gene expression microarray data: a comparison of variance modeling strategies","volume":"5","author":"M Jeanmougin","year":"2010","journal-title":"PLoS ONE"},{"key":"ref28","first-page":"H1670","article-title":"L-type calcium current in rod- and spindle-shaped myocytes isolated from rabbit atrioventricular node","volume":"267","author":"JC Hancox","year":"1994","journal-title":"Am J Physiol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"251","DOI":"10.4161\/chan.5.3.15266","article-title":"Functional roles of Ca<sub>v<\/sub>1.3, Ca<sub>v<\/sub>3.1 and HCN channels in automaticity of mouse atrioventricular cells: insights into the atrioventricular pacemaker mechanism","volume":"5","author":"L Marger","year":"2011","journal-title":"Channels"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1161\/01.CIR.0000152100.04087.DB","article-title":"Computer three-dimensional reconstruction of the sinoatrial node","volume":"111","author":"H Dobrzynski","year":"2005","journal-title":"Circulation"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"e000246","DOI":"10.1161\/JAHA.113.000246","article-title":"Functional, anatomical, and molecular investigation of the cardiac conduction system and arrhythmogenic atrioventricular ring tissue in the rat heart","volume":"2","author":"AJ Atkinson","year":"2013","journal-title":"J Am Heart Assoc"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.yjmcc.2010.12.017","article-title":"Molecular architecture of the human specialised atrioventricular conduction axis","volume":"50","author":"ID Greener","year":"2011","journal-title":"J Mol Cell Cardiol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"5543","DOI":"10.1073\/pnas.0935295100","article-title":"Functional role of L-type Ca<sub>v<\/sub>1.3 Ca<sup>2+<\/sup> channels in cardiac pacemaker activity","volume":"100","author":"ME Mangoni","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.yjmcc.2010.10.002","article-title":"Expression and roles of Ca<sub>v<\/sub>1.3 (\u03b11D) L-type Ca<sup>2+<\/sup> channel in atrioventricular node automaticity","volume":"50","author":"Q Zhang","year":"2011","journal-title":"J Mol Cell Cardiol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s004240050881","article-title":"Characteristics of a transient outward current (sensitive to 4-aminopyridine) in Ca<sup>2+<\/sup>-tolerant myocytes isolated from the rabbit atrioventricular node","volume":"438","author":"JS Mitcheson","year":"1999","journal-title":"Pflugers Arch"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"4149","DOI":"10.1113\/jphysiol.2013.255836","article-title":"Stabilization of K<sub>v<\/sub>4 protein by the accessory K<sup>+<\/sup> channel interacting protein 2 (KChIP2) subunit is required for the generation of native myocardial fast transient outward K<sup>+<\/sup> currents","volume":"591","author":"NC Foeger","year":"2013","journal-title":"J Physiol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1161\/01.RES.84.2.146","article-title":"Replacement by homologous recombination of the minK gene with lacZ reveals restriction of minK expression to the mouse cardiac conduction system","volume":"84","author":"S Kupershmidt","year":"1999","journal-title":"Circ Res"},{"key":"ref38","first-page":"891","article-title":"Structural and functional alterations in the atrioventricular node and atrioventricular ring tissue in ischaemia-induced heart failure","volume":"29","author":"J Yanni","year":"2014","journal-title":"Histol Histopathol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1161\/hc4201.097134","article-title":"Ionic remodeling of cardiac Purkinje cells by congestive heart failure","volume":"104","author":"W Han","year":"2001","journal-title":"Circulation"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1006\/jmcc.2000.1308","article-title":"Altered connexin expression in human congestive heart failure","volume":"33","author":"E Dupont","year":"2001","journal-title":"J Mol Cell Cardiol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1073\/pnas.1010122108","article-title":"Deep bradycardia and heart block caused by inducible cardiac-specific knockout of the pacemaker channel gene Hcn4","volume":"108","author":"M Baruscotti","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1096\/fj.02-0889com","article-title":"Hallmarks of ion channel gene expression in end-stage heart failure","volume":"17","author":"J Borlak","year":"2003","journal-title":"FASEB J"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0141452","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T12:50:21Z","timestamp":1540299021000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0141452"}},"subtitle":[],"editor":[{"given":"Alexander V","family":"Panfilov","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2015,10,28]]},"references-count":42,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2015,10,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0141452","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,28]]}}}